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Hepatitis C and HIV Co-Infection: New Drugs in Practice and in the Pipeline

  • Co-infections (C Benson, Section Editor)
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Abstract

HCV/HIV coinfection continues to represent a serious health issue with risk of liver disease progression and development of hepatocellular carcinoma. Pegylated interferon with ribavirin is approved for treatment but results are suboptimal and tolerability poor. First-generation HCV protease inhibitors appear to significantly improve HCV treatment response in the setting of HIV infection. Interactions with HIV protease inhibitors have been documented, but the significance of this in terms of adverse reactions and HCV or HIV viral breakthrough remains uncertain. Next generation agents hold the promise of even better efficacy, with improved dosing schedules and perhaps decreased risk of drug:drug interactions.

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References

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  1. Sherman KE, Thomas DL, Chung RT. Human immunodeficiency virus and liver disease forum 2010: conference proceedings. Hepatology. 2011;54:2245–53.

    Article  PubMed  Google Scholar 

  2. Bonacini M, Lin HJ, Hollinger FB. Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis C virus. J Acquir Immune Defic Syndr. 2001;26:340–4.

    Article  PubMed  CAS  Google Scholar 

  3. Benhamou Y, Bochet M, Di Martino V, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology. 1999;30:1054–8.

    Article  PubMed  CAS  Google Scholar 

  4. Sherman KE. HCV and HIV: a tale of two viruses. Rev Gastroenterol Disord. 2004;4 Suppl 1:S48–54.

    PubMed  Google Scholar 

  5. Sulkowski MS, Cheever L, Spach DH. A guide for evaluation and treatment of hepatitis C in adults coinfected with HIV. In: U.S. Department of Health and Human Services Health Resources and Services Administration; 2011.

  6. Chung RT, Andersen J, Volberding P, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351:451–9.

    Article  PubMed  CAS  Google Scholar 

  7. Torriani FJ, Chung RT. Peginterferon alpha-2a improved the hepatitis C virologic response in concurrent HIV and chronic hepatitis C virus infections. ACP journal club 2005;142:A12; author reply A3.

  8. Carrat F, Bani-Sadr F, Pol S, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. J Am Med Assoc. 2004;292:2839–48.

    Article  CAS  Google Scholar 

  9. Berenguer J, Gonzalez-Garcia J, Lopez-Aldeguer J, et al. Pegylated interferon {alpha}2a plus ribavirin versus pegylated interferon {alpha}2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients. J Antimicrob Chemother. 2009;63:1256–63.

    Article  PubMed  CAS  Google Scholar 

  10. Shire NJ, Welge JA, Sherman KE. Response rates to pegylated interferon and ribavirin in HCV/HIV coinfection: a research synthesis. J Viral Hepat. 2007;14:239–48.

    Article  PubMed  CAS  Google Scholar 

  11. •• Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405–16. This paper describes the phase 3 pivotal trial that led to approval of telaprevir for HCV monoinfection treatment in treatment-naive patients.

    Article  PubMed  CAS  Google Scholar 

  12. • Sherman KE, Flamm SL, Afdhal NH, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med. 2011;365:1014–24. This phase 3 study established that response-guided therapy represents a rational and highly efficacious methodology for the treatment of HCV using newer DAA agents.

    Article  PubMed  CAS  Google Scholar 

  13. •• Poordad F, McCone Jr J, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–206. This study described the phase 3 pivotal trial that led to approval of boceprevir for HCV monoinfection treatment in treatment-naive patients.

    Article  PubMed  CAS  Google Scholar 

  14. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207–17.

    Article  PubMed  CAS  Google Scholar 

  15. Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417–28.

    Article  PubMed  CAS  Google Scholar 

  16. Montaudie H, Passeron T, Cardot-Leccia N, Sebbag N, Lacour JP. Drug rash with eosinophilia and systemic symptoms due to telaprevir. Dermatology. 2010;221:303–5.

    Article  PubMed  CAS  Google Scholar 

  17. Sulkowski MS, Pol S, Cooper, C, Fainboim H, Slim J, Rivero A, et al. Boceprevir + pegylated interferon + ribavirin for the treatment of HCV/HIV co-infected patients: End of treatment (Week 48) interim results. In: CROI. Seattle, WA; 2012.

  18. Dieterich D, Soriano V, Sherman KE, Girard P-M, Rockstroh J, Adiwijaya B, et al. Telaprevir in combination with pegylated interferon alfa 2a + ribavirin in HCV/HIV coinfected patients: A 24-week treatment interim analysis. In: 19th Conference on Retroviruses and Opportunistic Infections (CROI); 2012:Abs. 46.

  19. Kasserra C, Hughes E, Treitel M, Gupta S, O’Mara E. Clinical pharmacology of BOC: metabolism, excretion, and drug–drug Interactions. In: 18th Conference on Retroviruses and Opportunistic Infections. Boston; 2011.

  20. Wilby KJ, Greanya ED, Ford JA, Yoshida EM, Partovi N. A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients. Ann Hepatol. 2012;11:179–85.

    PubMed  CAS  Google Scholar 

  21. Kiser JJ, Burton JR, Anderson PL, Everson GT. Review and management of drug interactions with boceprevir and telaprevir. Hepatology 2012.

  22. Dianzani F, Rozera G, Abbate I, et al. Interferon may prevent HIV viral rebound after HAART interruption in HIV patients. J Interferon Cytokine Res. 2008;28:1–3.

    Article  PubMed  CAS  Google Scholar 

  23. van Heeswijk R, Vandevoorde A, Boogaerts G, Vangeneugden T, de Paepe E, Polo R, et al. Pharmacokinetic Interactions between ARV Agents and the Investigational HCV Protease Inhibitor TVR in Healthy Volunteers. In: CROI. Boston; 2011.

  24. Sherman KE, Fleischer R, Laessig K, Murray J, Tauber W, Birnkrant D. Development of novel agents for the treatment of chronic hepatitis C infection: Summary of the FDA Antiviral Products Advisory Committee recommendations. Hepatology. 2007;46:2014–20.

    Article  PubMed  CAS  Google Scholar 

  25. Zamor PJ, Rouster S, Sherman KE. HCV NS3 mutations in HCV-HIV coinfected and HCV monoinfected subjects. In: AASLD. Boston; 2010.

  26. Sherman KE, Sulkowski MS, Zoulim F, et al. Follow-up of Svr durability and viral resistance in patients with chronic hepatitis C treated with telaprevir-based regimens: interim analysis of the extend study. Hepatology. 2011;54:485a–6a.

    Article  Google Scholar 

  27. Brass C, Barnard RJO, Howe JA, et al. Sustained virologic response and boceprevir resistance-associated variants observed in patients infected with Hcv genotype 1a/1b when treated with boceprevir plus peginterferon alfa-2b/ribavirin. J Hepatol. 2011;54:S471–2.

    Article  Google Scholar 

  28. Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798–801.

    Article  PubMed  CAS  Google Scholar 

  29. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.

    Article  PubMed  CAS  Google Scholar 

  30. Abu Dayyeh BK, Gupta N, Sherman KE, de Bakker PIW, Chung RT. A5178 ACTG. IL28B alleles exert an additive dose effect when applied to HCV-HIV coinfected persons undergoing peginterferon and ribavirin therapy. PLoS One 2011;6.

  31. Rallon NI, Naggie S, Benito JM, et al. Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS. 2010;24:F23–9.

    Article  PubMed  CAS  Google Scholar 

  32. Poordad F, Bronowicki JP, Gordon SC, et al. IL28B polymorphism predicts virologic response in patients with hepatitis C genotype 1 treated with boceprevir (Boc) combination therapy. Gastroenterology. 2011;140:S941-S.

    Google Scholar 

  33. Jacobson IM, Catlett I, Marcellin P, Bzowej NH, Muir AJ, Adda N, et al. Telaprevir substantially improved SVR rates across all IL28B genotypes in the advance trial. In: EASL. Berlin; 2011.

  34. Crabbe R, Vuagniaux G, Dumont JM, Nicolas-Metral V, Marfurt J, Novaroli L. An evaluation of the cyclophilin inhibitor Debio 025 and its potential as a treatment for chronic hepatitis C. Expert Opin Investig Drugs. 2009;18:211–20.

    Article  PubMed  CAS  Google Scholar 

  35. Flisiak R, Horban A, Gallay P, et al. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology. 2008;47:817–26.

    Article  PubMed  CAS  Google Scholar 

  36. Flisiak R, Pawlotsky JM, Crabbe R, et al. Once daily alisporivir (Deb025) plus PegIFNalfa2a/Ribavirin results in superior sustained virologic response (Svr24) in chronic hepatitis C genotype 1 treatment naive patients. J Hepatol. 2011;54:S2-S.

    Google Scholar 

  37. Flisiak R, Jaroszewicz J, Flisiak I, Łapiński T. Update on alisporivir in treatment of viral hepatitis C. Expert Opin Investig Drugs. 2012;21:375–82.

    Article  PubMed  CAS  Google Scholar 

  38. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216–24.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This project was supported by funding from the NIDDK K24 DK070528 to KES. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

Disclosure

C. L. Jennings: consultant to Three Rivers Pharmaceuticals and speakers’ bureaus for Vertex Pharmaceuticals; K. E. Sherman: consultant to Vertex, BMS, Merck, SciClone, GSK, Three Rivers, J&J, Regulus, Valeant, Anadys, Schering, Baxter, Astellas, Boehringer-Ingelheim, Fibrogen, and Abbott.

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  1. University of Cincinnati College of Medicine/UCHealth, 231 Albert Sabin Way, Cincinnati, OH, 45267-0595, USA

    Carrie L. Jennings & Kenneth E. Sherman

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  1. Carrie L. Jennings
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  2. Kenneth E. Sherman
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Correspondence to Kenneth E. Sherman.

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Jennings, C.L., Sherman, K.E. Hepatitis C and HIV Co-Infection: New Drugs in Practice and in the Pipeline. Curr HIV/AIDS Rep 9, 231–237 (2012). https://doi.org/10.1007/s11904-012-0122-z

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  • DOI: https://doi.org/10.1007/s11904-012-0122-z

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